The emphasis of this proposal is to correlate morphogenesis of the development of the prostate with that of the biochemical characteristics of this gland. The concept that stromal-epithelial interactions serve as a prerequisite for appropriate morphogenesis, hence the biochemical responses, will be developed. The ultimate goal of this proposal is to elucidate the roles of prostatic stroma (both directive and permissive) on epithelial development and differentiation. The possible roles of stroma in the development of human benign prostatic hyperplasia will be critically examined. The objectives and the approach of this proposal are outlined: 1) To develop and perfect techniques of separating prostatic stroma from its epithelium. Priority will be given to the development of an adequate density gradient centrifugation technique and appropriate histochemical and biochemical methods for determining the purity of a given cell population. 2) To investigate the inductive potential of prostatic stroma on epithelial differentiation. Emphasis will be placed on delineation of mechanisms of such induction. For example, the possible involvement of androgen receptor mechanism, the macromolecular synthesis, and/or the androgen metabolic potential of both stroma and epithelium will be studied. 3) To determine the mode of action of neonatal or prepubertal sex steroids on the development of rat accessory sex organs. The nature of certain permanent sex steroid(s)-induced effects on the development of these glands at adulthood will be studied. 4) To determine the role of androgen receptor during prostatic morphogenesis. Androgen receptor activity will be assayed in tissue recombinants composed of epithelium and stroma of urogenital sinuses from Tfm and wild-type mice. 5) To critically examine the concept of Dr. McNeal that human benign prostatic hyperplasia represents a reactivation of the embryonic potential of the stroma component in the periurethral region of this gland.